Document Detail


UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells.
MedLine Citation:
PMID:  20849830     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cardiac steroids are used to treat various diseases including congestive heart failure and cancer. The aim of this study was to investigate the anti-leukemic activity of UNBS1450, a hemi-synthetic cardenolide belonging to the cardiac steroid glycoside family. Here, we report that, at low nanomolar concentrations, UNBS1450 induces apoptotic cell death. Subsequently, we have investigated the molecular mechanisms leading to apoptosis activation. Our results show that UNBS1450 inhibits NF-κB transactivation and triggers apoptosis by cleavage of pro-caspases 8, 9 and 3/7, by decreasing expression of anti-apoptotic Mcl-1 and by recruitment of pro-apoptotic Bak and Bax protein eventually resulting in cell death.
Authors:
Tom Juncker; Claudia Cerella; Marie-Hélène Teiten; Franck Morceau; Marc Schumacher; Jenny Ghelfi; François Gaascht; Michael Schnekenburger; Estelle Henry; Mario Dicato; Marc Diederich
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-21
Journal Detail:
Title:  Biochemical pharmacology     Volume:  81     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2010-12-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  13-23     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Cardenolides / chemistry,  pharmacology*
Cell Line
Gene Expression Regulation, Neoplastic
Humans
Leukemia / drug therapy*
Molecular Structure
Neoplasm Proteins / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Cardenolides; 0/Neoplasm Proteins; 0/UNBS 1450

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